Known methods for altering the structure of a polypeptide or protein typically involve changing the physical conditions of a sample that contains the polypeptide. The sample may be heated or cooled, or the pH or salt concentration of the sample may be varied. Any one of these changes may affect the structure of a folded polypeptide. However, because they are applied globally, such changes may also affect the structures of other components of the sample. Consequently, the functional properties of all biomolecules in the sample may be affected.
Conventional techniques are also global with respect to a polypeptide molecule itself, affecting the molecule as a whole rather than a localized portion thereof. For example, the effects of a gross environmental change, such as heating, will affect the entire molecule uniformly. Even chemical reagents directed toward particular moieties will affect such moieties wherever they occur along the molecule. As a result, precise control over individual molecular entities or portions thereof has not heretofore been feasible.
Nonetheless, in many practical settings there is a need to control the function of a specific protein that is present in a heterogeneous solution containing other proteins and nucleic acids. There is also a need in the art for methods and compositions for directly or remotely altering the properties of a protein, or a portion of a protein without changing any other components of a sample containing the protein.